Single-molecule measurements reveal that PARP1 condenses DNA by loop stabilization

Poly(ADP-ribose) polymerase 1 (PARP1) is an abundant nuclear enzyme that plays important roles in DNA repair, chromatin organization and transcription regulation. Although binding and activation of PARP1 by DNA damage sites has been extensively studied, little is known about how PARP1 binds to long stretches of undamaged DNA and how it could shape chromatin architecture. Here, using single-molecule techniques, we show that PARP1 binds and condenses undamaged, kilobase-length DNA subject to sub-piconewton mechanical forces. Stepwise decondensation at high force and DNA braiding experiments show that the condensation activity is due to the stabilization of DNA loops by PARP1. PARP inhibitors do not affect the level of condensation of undamaged DNA but act to block condensation reversal for damaged DNA in the presence of NAD+. Our findings suggest a mechanism for PARP1 in the organization of chromatin structure

Psychological Indicators and Perceptions of Adolescents in Residential Care

Abstract The institutionalization of adolescents has been mentioned in the literature with positive and negative aspects. This study investigated 61 adolescents in residential care aiming to evaluate psychological problems and perceptions related to the care, using interviews and the YSR. Data was evaluated using quantitative and qualitative analysis, using gender, age and length of institutionalization as variables. Results indicated clinical scores for psychological problems, except for externalizing problems, in younger girls recently taken into care and older boys institutionalized for longer periods. The perceptions about the care were negative or indifferent; elements of positivity were expressed by adolescents institutionalized for longer periods. Instability in the permanence in the care service and the reasons for having been taken into care were manifested with psychological distress. There were few contacts with the family of origin; the adolescents mentioned the importance of their families and the desire to leave the institution. Members of the institutional teams were indicated as sources of care and protection. This study reflects the challenges for the positive development of this population

Impairment of Adenosinergic System in Rett syndrome: Novel Therapeutic Target to Boost BDNF Signalling

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through A2AR it potentiates BDNF synaptic actions in healthy animals. We thus characterized several hallmarks of the adenosinergic and BDNF signalling in RTT and explored whether A2AR activation could boost BDNF actions. For this study, the RTT animal model, the Mecp2 knockout (Mecp2-/y) (B6.129P2 (C)-Mecp2tm1.1Bird/J) mouse was used. Whenever possible, parallel data was also obtained from post-mortem brain samples from one RTT patient. Ex vivo extracellular recordings of field excitatory post-synaptic potentials in CA1 hippocampal area were performed to evaluate synaptic transmission and long-term potentiation (LTP). RT-PCR was used to assess mRNA levels and Western Blot or radioligand binding assays were performed to evaluate protein levels. Changes in cortical and hippocampal adenosine content were assessed by liquid chromatography with diode array detection (LC/DAD). Hippocampal ex vivo experiments revealed that the facilitatory actions of BDNF upon LTP is absent in Mecp2-/y mice and that TrkB full-length (TrkB-FL) receptor levels are significantly decreased. Extracts of the hippocampus and cortex of Mecp2-/y mice revealed less adenosine amount as well as less A2AR protein levels when compared to WT littermates, which may partially explain the deficits in adenosinergic tonus in these animals. Remarkably, the lack of BDNF effect on hippocampal LTP in Mecp2-/y mice was overcome by selective activation of A2AR with CGS21680. Overall, in Mecp2-/y mice there is an impairment on adenosinergic system and BDNF signalling. These findings set the stage for adenosine-based pharmacological therapeutic strategies for RTT, highlighting A2AR as a therapeutic target in this devastating pathology.info:eu-repo/semantics/publishedVersio

First occurrence of an autochthonous canine case of Leishmania (Leishmania) infantum chagasi in the municipality of Campinas, State of São Paulo, Brazil

An autochthonous case of visceral leishmaniasis is reported in a dog (Canis familiaris) as an apparently natural infection in a non-endemic area. DNA obtained from spleen and liver samples produced the expected fragment in a Leishmania-specific rDNA-based nested-PCR assay. The PCR product, a 490 bp fragment, was sequenced and the nucleotide sequence was identical to that of Leishmania (Leishmania) infantum chagasi. These results are surprising since no autochthonous human or canine cases of visceral leishmaniasis have ever been reported in this municipality. This case suggests that natural transmission of this disease is occurring in this area

Prevention of skin reactions due to teletherapy in women with breast cancer: a comprehensive review

One of the possible courses of cancer treatment is teletherapy, and one of the most important adverse side effects are skin reactions, an ailment more commonly called radiodermatitis. The main purpose of this study is to analyze knowledge of the evidence about topical products used in the prevention of radiodermatitis, to support care delivery to women with breast cancer during teletherapy. The research method used here is the comprehensive literature review. Four databases were used to select the bibliography. The sample consists of 15 articles. The data shows that, among the topical products analyzed here, Calendula, corticosteroids and Xclair have shown significant protective effects, underlining their actions. The lack of articles published in Brazil highlights the need for further research in this area, seeking better care quality through the use of products with scientifically proven efficiency.Teleterapia está entre las modalidades de tratamiento para el cáncer y uno de sus principales efectos adversos son reacciones de la piel, comúnmente llamado radiodermatitis. Este estudio objetivó analizar el conocimiento acerca de los productos tópicos utilizados para la prevención de la radiodermatitis que justifiquen la atención en teleterapia en mujeres con cáncer de mama. Se adoptó como método de investigación la revisión integradora de la literatura. Para la selección de los artículos se utilizaron cuatro bases de datos. La muestra fue constituida por 15 artículos. Los datos muestran que entre los productos tópicos analizados la caléndula, esteroides y Clair X tuvo un efecto protector significativo, destacando así por sus acciones. La ausencia de artículos publicados en Brasil se centra en la necesidad de seguir investigando para mejorar la calidad de la atención mediante el uso de productos con una eficacia científicamente probada.Dentre as modalidades de tratamento para o câncer está a teleterapia, e um dos principais efeitos adversos dessa modalidade são as reações de pele, comumente chamadas radiodermatites. O presente estudo teve como objetivo analisar o conhecimento sobre as evidências acerca de produtos tópicos, utilizados na prevenção de radiodermatite, que fundamente o cuidado em teleterapia direcionado a mulheres com câncer de mama. Adotou-se como método de pesquisa a revisão integrativa da literatura. Para a seleção da bibliografia utilizaram-se quatro bases de dados. A amostra constitui-se de 15 artigos. Os dados demonstram que, dentre os produtos tópicos analisados, a calêndula, os corticoesteroides e o Xclair tiveram efeito protetor significante, destacando-se, assim, pelas suas ações. A ausência de artigos publicados no Brasil mostra a necessidade de mais pesquisas nessa área, visando a melhor qualidade na assistência a mulheres com câncer de mama, por meio da utilização de produtos com eficácia comprovada cientificamente

Decline in Diarrhea Mortality and Admissions after Routine Childhood Rotavirus Immunization in Brazil: A Time-Series Analysis

A time series analysis by Manish Patel and colleagues shows that the introduction of rotavirus vaccination in Brazil is associated with reduced diarrhea-related deaths and hospital admissions in children under 5 years of age